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ATDC 对于 KRAS 诱导的胰腺肿瘤发生是必需的。

ATDC is required for the initiation of KRAS-induced pancreatic tumorigenesis.

机构信息

Department of Surgery, New York University School of Medicine, New York, New York 10016, USA.

Perlmutter Cancer Center, NYU Langone Medical Center, New York University, New York, New York 10016, USA.

出版信息

Genes Dev. 2019 Jun 1;33(11-12):641-655. doi: 10.1101/gad.323303.118. Epub 2019 May 2.

DOI:10.1101/gad.323303.118
PMID:31048544
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6546061/
Abstract

Pancreatic adenocarcinoma (PDA) is an aggressive disease driven by oncogenic KRAS and characterized by late diagnosis and therapeutic resistance. Here we show that deletion of the ataxia-telangiectasia group D-complementing () gene, whose human homolog is up-regulated in the majority of pancreatic adenocarcinoma, completely prevents PDA development in the context of oncogenic KRAS. ATDC is required for KRAS-driven acinar-ductal metaplasia (ADM) and its progression to pancreatic intraepithelial neoplasia (PanIN). As a result, mice lacking ATDC are protected from developing PDA. Mechanistically, we show ATDC promotes ADM progression to PanIN through activation of β-catenin signaling and subsequent SOX9 up-regulation. These results provide new insight into PDA initiation and reveal ATDC as a potential target for preventing early tumor-initiating events.

摘要

胰腺导管腺癌（PDA）是一种侵袭性疾病，由致癌 KRAS 驱动，并以晚期诊断和治疗抵抗为特征。在这里，我们表明，在致癌 KRAS 的背景下，缺失共济失调毛细血管扩张症组 D 补体（）基因的缺失完全阻止了 PDA 的发展，其人类同源物在大多数胰腺导管腺癌中上调。ATDC 是 KRAS 驱动的腺泡-导管化生（ADM）及其进展为胰腺上皮内瘤变（PanIN）所必需的。因此，缺乏 ATDC 的小鼠免于发展为 PDA。从机制上讲，我们表明 ATDC 通过激活 β-catenin 信号和随后的 SOX9 上调促进 ADM 进展为 PanIN。这些结果为 PDA 的起始提供了新的见解，并揭示了 ATDC 作为预防早期肿瘤起始事件的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94c7/6546061/beb4939f24bb/641f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94c7/6546061/6982b713cadb/641f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94c7/6546061/3735e8f1f946/641f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94c7/6546061/7453da962554/641f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94c7/6546061/aaf66a2c1b2b/641f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94c7/6546061/2904b05b2d8d/641f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94c7/6546061/6ce39fc3dffa/641f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94c7/6546061/beb4939f24bb/641f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94c7/6546061/6982b713cadb/641f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94c7/6546061/3735e8f1f946/641f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94c7/6546061/7453da962554/641f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94c7/6546061/aaf66a2c1b2b/641f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94c7/6546061/2904b05b2d8d/641f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94c7/6546061/6ce39fc3dffa/641f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94c7/6546061/beb4939f24bb/641f07.jpg

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2
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3
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4
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5
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6
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7
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